Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000114430 | SCV002296515 | uncertain significance | Amyotrophic lateral sclerosis type 21 | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 115 of the MATR3 protein (p.Phe115Cys). This variant is present in population databases (rs587777300, gnomAD 0.003%). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis and/or dementia (PMID: 24686783). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 126561). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MATR3 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MATR3 function (PMID: 24686783, 26528920, 29109432, 30015619, 30563574, 31019288). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| OMIM | RCV000114430 | SCV000148373 | pathogenic | Amyotrophic lateral sclerosis type 21 | 2014-03-30 | no assertion criteria provided | literature only |